Synthesis of 3-O-Carboxyalkyl Morphine Derivatives and Characterization of Their Acid-Base Properties |
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Authors: | István Köteles Károly Mazák Gergő Tóth Péter Horváth Eszter Kiss Boglárka Tűz Sándor Hosztafi |
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Affiliation: | Department of Pharmaceutical Chemistry, Semmelweis University, Hőgyes Endre u. 9., H-1092 Budapest, Hungary |
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Abstract: | The C-3 phenolic hydroxy group containing morphine derivatives (morphine, oxymorphone, naloxone, naltrexone) are excellent candidates for the synthesis of 3-O-functionalized molecules. Achieving free carboxylic group containing derivatives gives the opportunity for further modification and conjugation that could be used for immunization and immunoassays. For this purpose ethyl bromo- and chloroacetate can be used as O-alkylating agents. Hydrolyzing the products affords the appropriate free carboxylic group containing 3-O-carboxyalkyl derivatives. As these molecules contain an acidic and a basic functional group the protonation macro- and microconstants were determined too, using pH-potentiometry and NMR-pH titration, beside fully characterizing their structure using IR, CD, NMR and HR-MS measurements. |
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Keywords: | morphine O ligands hapten protonation NMR spectroscopy |
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